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1.
Nature ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977018

RESUMO

Two-dimensional (2D)/three-dimensional (3D) perovskite heterostructures have played a key role in advancing the performance of perovskite solar cells (PSCs)1,2. However, the migration of cations between 2D and 3D layers results in the disruption of octahedral networks that leads to degradation in performance over time3,4. We hypothesized that perovskitoids, with robust organic-inorganic networks enabled by edge- and face-sharing, could impede ion migration. We explored a set of perovskitoids of varying dimensionality, and found that cation migration within perovskitoid/perovskite heterostructures was suppressed compared to the 2D/3D perovskite case. Increasing the dimensionality of perovskitoids improves charge transport when they are interfaced with 3D perovskite surfaces - this the result of enhanced octahedral connectivity and out-of-plane orientation. The 2D perovskitoid (A6BfP)8Pb7I22 (A6BfP: N-aminohexyl-benz[f]-phthalimide) provides efficient passivation of perovskite surfaces and enables uniform large-area perovskite films. Devices based on perovskitoid/perovskite heterostructures achieve a certified quasi-steady-state power conversion efficiency of 24.6% for centimeter-area PSCs. We removed the fragile hole transport layers and showed stable operation of the underlying perovskitoid/perovskite heterostructure at 85°C for 1,250 hours for encapsulated large-area devices in an air ambient.

2.
PLoS Pathog ; 20(7): e1012170, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39074144

RESUMO

While Merkel cell polyomavirus (MCPyV or MCV) is an abundant virus frequently shed from healthy skin, it is one of the most lethal tumor viruses in immunocompromised individuals, highlighting the crucial role of host immunity in controlling MCPyV oncogenic potential. Despite its prevalence, very little is known about how MCPyV interfaces with the host immune response to maintain asymptomatic persistent infection and how inadequate control of MCPyV infection triggers MCC tumorigenesis. In this study, we discovered that the MCPyV protein, known as the Alternative Large Tumor Open Reading Frame (ALTO), also referred to as middle T, effectively primes and activates the STING signaling pathway. It recruits Src kinase into the complex of STING downstream kinase TBK1 to trigger its autophosphorylation, which ultimately activates the subsequent antiviral immune response. Combining single-cell analysis with both loss- and gain-of-function studies of MCPyV infection, we demonstrated that the activity of ALTO leads to a decrease in MCPyV replication. Thus, we have identified ALTO as a crucial viral factor that modulates the STING-TBK1 pathway, creating a negative feedback loop that limits viral infection and maintains a delicate balance with the host immune system. Our study reveals a novel mechanism by which a tumorigenic virus-encoded protein can link Src function in cell proliferation to the activation of innate immune signaling, thereby controlling viral spread, and sustaining persistent infection. Our previous findings suggest that STING also functions as a tumor suppressor in MCPyV-driven oncogenesis. This research provides a foundation for investigating how disruptions in the finely tuned virus-host balance, maintained by STING, could alter the fate of MCPyV infection, potentially encouraging malignancy.


Assuntos
Poliomavírus das Células de Merkel , Infecções por Polyomavirus , Proteínas Serina-Treonina Quinases , Infecções Tumorais por Vírus , Proteínas Serina-Treonina Quinases/metabolismo , Infecções por Polyomavirus/metabolismo , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Humanos , Infecções Tumorais por Vírus/metabolismo , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Carcinoma de Célula de Merkel/virologia , Carcinoma de Célula de Merkel/metabolismo , Proteínas de Membrana/metabolismo , Transdução de Sinais , Proteínas Virais/metabolismo , Replicação Viral , Neoplasias Cutâneas/virologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/imunologia , Animais
3.
Acta Biomater ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39059731

RESUMO

Limited treatments and a lack of appropriate animal models have spurred the study of scaffolds to mimic lung disease in vitro. Decellularized human lung and its application in extracellular matrix (ECM) hydrogels has advanced the development of these lung ECM models. Controlling the biochemical and mechanical properties of decellularized ECM hydrogels continues to be of interest due to inherent discrepancies of hydrogels when compared to their source tissue. To optimize the physiologic relevance of ECM hydrogel lung models without sacrificing the native composition we engineered a binary fabrication system to produce a Hybridgel composed of an ECM hydrogel reinforced with an ECM cryogel. Further, we compared the effect of ECM-altering disease on the properties of the gels using elastin poor Chronic Obstructive Pulmonary Disease (COPD) vs non-diseased (ND) human lung source tissue. Nanoindentation confirmed the significant loss of elasticity in hydrogels compared to that of ND human lung and further demonstrated the recovery of elastic moduli in ECM cryogels and Hybridgels. These findings were supported by similar observations in diseased tissue and gels. Successful cell encapsulation, distribution, cytotoxicity, and infiltration were observed and characterized via confocal microscopy. Cells were uniformly distributed throughout the Hybridgel and capable of survival for 7 days. Cell-laden ECM hybridgels were found to have elasticity similar to that of ND human lung. Compositional investigation into diseased and ND gels indicated the conservation of disease-specific elastin to collagen ratios. In brief, we have engineered a composited ECM hybridgel for the 3D study of cell-matrix interactions of varying lung disease states that optimizes the application of decellularized lung ECM materials to more closely mimic the human lung while conserving the compositional bioactivity of the native ECM. STATEMENT OF SIGNIFICANCE: The lack of an appropriate disease model for the study of chronic lung diseases continues to severely inhibit the advancement of treatments and preventions of these otherwise fatal illnesses due to the inability to recapture the biocomplexity of pathologic cell-ECM interactions. Engineering biomaterials that utilize decellularized lungs offers an opportunity to deconstruct, understand, and rebuild models that highlight and investigate how disease specific characteristics of the extracellular environment are involved in driving disease progression. We have advanced this space by designing a binary fabrication system for a ECM Hybridgel that retains properties from its source material required to observe native matrix interactions. This design simulates a 3D lung environment that is both mechanically elastic and compositionally relevant when derived from non-diseased tissue and pathologically diminished both mechanically and compositionally when derived from COPD tissue. Here we describe the ECM hybridgel as a model for the study of cell-ECM interactions involved in COPD.

5.
bioRxiv ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38948803

RESUMO

About one-third of all human cancers encode abnormal RAS proteins locked in a constitutively activated state to drive malignant transformation and uncontrolled tumor growth. Despite progress in development of small molecules for treatment of mutant KRAS cancers, there is a need for a pan-RAS inhibitor that is effective against all RAS isoforms and variants and that avoids drug resistance. We have previously shown that the naturally occurring bacterial enzyme RAS/RAP1-specific endopeptidase (RRSP) is a potent RAS degrader that can be re-engineered as a biologic therapy to induce regression of colorectal, breast, and pancreatic tumors. Here, we have developed a strategy for in vivo expression of this RAS degrader via mRNA delivery using a synthetic nonviral gene delivery platform composed of the poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-b-PPS) block copolymer conjugated to a dendritic cationic peptide (PPDP2). Using this strategy, PPDP2 is shown to deliver mRNA to both human and mouse pancreatic cells resulting in RRSP gene expression, activity, and loss of cell proliferation. Further, pancreatic tumors are reduced with residual tumors lacking detectable RAS and phosphorylated ERK. These data support that mRNA-loaded synthetic nanocarrier delivery of a RAS degrader can interrupt the RAS signaling system within pancreatic cancer cells while avoiding side effects during therapy.

6.
Org Lett ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39024514

RESUMO

This report describes a method for the photochemical Cu-mediated fluorination of aryl iodides with AgF via putative aryl radical (Ar•) intermediates. It involves irradiating an aryl iodide with UVB light (λmax = 313 nm) in the presence of a mixture of CuI and CuII salts and AgF. Under these conditions, fluorination proceeds at room temperature for substrates containing diverse substituents, including alkoxy and alkyl groups, ketones, esters, sulfonate esters, sulfonamides, and protected amines. This method has been translated to radiofluorination using a combination of K18F, K3PO4, and AgOTf.

7.
Food Chem ; 457: 140142, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38936122

RESUMO

Litchi (Litchi chinensis Sonn.) is a tropical fruit with various health benefits. The objective of this study is to present a thorough analysis of the cancer preventive and anticancer therapeutic properties of litchi constituents and phytocompounds. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria were followed in this work. Various litchi extracts and constituents were studied for their anticancer effects. In vitro studies showed that litchi-derived components reduced cell proliferation, induced cytotoxicity, and promoted autophagy via increased cell cycle arrest and apoptosis. Based on in vivo studies, litchi flavonoids and other extracted constituents significantly reduced tumor size, number, volume, and metastasis. Major signaling pathways impacted by litchi constituents were shown to stimulate proapoptotic, antiproliferative, and antimetastatic activities. Despite promising antineoplastic activities, additional research, especially in vivo and clinical studies, is necessary before litchi-derived products and phytochemicals can be used for human cancer prevention and intervention.

8.
Cureus ; 16(5): e60382, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38882954

RESUMO

Gallbladder perforation is a rare complication of acute cholecystitis that is associated with significant morbidity and mortality. Many cases of gallbladder perforation are not diagnosed until surgery, as the physical symptoms closely mimic acute cholecystitis. Gallbladder perforation is most common among older males with associated comorbidities, and preoperative assessment of comorbidities, particularly cardiac, is critical to determine the appropriate clinical course. We report a case of a 77-year-old male who presented initially with low blood pressure and right upper quadrant pain (RUQ) after not feeling well for five days. CT of the abdomen/pelvis with IV contrast demonstrated acute perforated cholecystitis, and general surgery was consulted for a cholecystectomy. Due to the patient's past medical history of severe aortic stenosis (AS), cholecystectomy was deferred and a cholecystostomy tube was placed by interventional radiology. This report aims to provide an example of a case of perforated cholecystitis with sepsis and how it can be diagnosed and managed non-surgically in the presence of pre-existing severe AS.

9.
Br J Cancer ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914804

RESUMO

BACKGROUND: Early phase clinical trials in Oncology represent a subspecialised area where UK patient selection is influenced by access to Experimental Cancer Medicine Centres (ECMCs). Equity of access with respect to social determinants of health (SDoH) were explored for two major ECMCs. METHODS: A retrospective cohort study including all referrals to Newcastle and Manchester ECMCs in 2021 was completed. Consent to screening or pre-screening was stratified against SDoH characteristics, including: Index of Multiple Deprivation (IMD) decile, ethnicity and distance to centre. RESULTS: 1243 patients were referred for trials. IMD quintile 1 (most deprived) patients had reduced likelihood of referral compared to expected population models (OR, 0.67; 95% CI: 0.55 to 0.80, p = <0.0001). IMD quintile 5 (least deprived) had increased likelihood of referral (OR, 1.46; 95% CI: 1.17 to 1.82, p = 0.0007). Living beyond median distance from Manchester reduced the likelihood of consenting to trials (OR, 0.72; 95% CI: 0.55 to 0.94, p = 0.015). Ethnicity data represented a White British propensity. CONCLUSIONS: Inequalities in socioeconomic and geographic factors influence referral and enrolment to early phase clinical trials in Northern England. This has implications for equity of access and generalisability of trial results internationally and warrants further study.

10.
IEEE Trans Biomed Eng ; PP2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38857143

RESUMO

Real-time estimation of patient cardiovascular states, including cardiac output and systemic vascular resistance, is necessary for personalized hemodynamic monitoring and management. Highly invasive measurements enable reliable estimation of these states but increase patient risk. Prior methods using minimally invasive measurements reduce patient risk but have produced unreliable estimates limited due to trade-offs in accuracy and time resolution. Our objective was to develop an approach to estimate cardiac output and systemic vascular resistance with both a high time resolution and high accuracy from minimally invasive measurements. Using the two-element Windkessel model, we formulated a state-space method to estimate a dynamic time constant - the product of systemic vascular resistance and compliance - from arterial blood pressure measurements. From this time constant, we derived proportional estimates of systemic vascular resistance and cardiac output. We then validated our method with a swine cardiovascular dataset. Our estimates produced using arterial blood pressure measurements not only closely align with those using highly invasive measurements, but also closely align when derived from three separate locations on the arterial tree. Moreover, our estimates predictably change in response to standard cardiovascular drugs. Overall, our approach produces reliable, real-time estimates of cardiovascular states crucial for monitoring and control of the cardiovascular system.

11.
Am J Sports Med ; 52(8): 2021-2028, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38857043

RESUMO

BACKGROUND: Physical therapy is frequently utilized in the postoperative care of femoroacetabular impingement syndrome (FAIS). There has been limited research into the efficacy of a structured home exercise program (HEP) compared with formal physical therapy (FPT) in this patient population. PURPOSE/HYPOTHESIS: The purpose was to evaluate the short-term outcomes of patients utilizing FPT versus an HEP after hip arthroscopic surgery for FAIS. It was hypothesized that both groups would show similar improvements regarding outcome scores, which would improve significantly compared with their preoperative scores. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Patients undergoing hip arthroscopic surgery for FAIS at a single center between October 2020 and October 2021 were prospectively enrolled. Patients were allowed to self-select FPT or an HEP and were administered a survey preoperatively and at 1 month, 3 months, 6 months, and 12 months postoperatively. The survey included the Single Assessment Numeric Evaluation, visual analog scale for pain, 12-item International Hip Outcome Tool, Patient-Reported Outcomes Measurement Information System Physical Function, and patient satisfaction with physical therapy and overall care. Statistical analysis was conducted between the 2 groups and within groups to compare preoperative and postoperative scores. RESULTS: The patients' mean age was 32.6 ± 10.4 years, with 47.2% being female and 57.4% choosing the HEP. At 12 months postoperatively, no significant differences were reported between the FPT and HEP groups regarding the Single Assessment Numeric Evaluation score (P = .795), visual analog scale for pain score (P > .05), Patient-Reported Outcomes Measurement Information System Physical Function T-score (P = .699), 12-item International Hip Outcome Tool score (P = .582), and patient satisfaction (P > .05). Outcome scores at 12 months postoperatively were significantly improved from the preoperative scores across all measures in both groups (P < .001). CONCLUSION: There were no significant differences regarding patient outcomes between FPT and the HEP at 1-year follow-up after hip arthroscopic surgery for FAIS when patients selected their own treatment, with both groups demonstrating significant improvements in their outcome scores from their preoperative values. These findings suggest that a structured HEP may be a viable alternative to FPT after hip arthroscopic surgery in patients who prefer a self-directed rehabilitation program.


Assuntos
Artroscopia , Terapia por Exercício , Impacto Femoroacetabular , Humanos , Feminino , Masculino , Impacto Femoroacetabular/cirurgia , Impacto Femoroacetabular/reabilitação , Adulto , Estudos Prospectivos , Terapia por Exercício/métodos , Pessoa de Meia-Idade , Satisfação do Paciente , Medidas de Resultados Relatados pelo Paciente , Modalidades de Fisioterapia , Resultado do Tratamento , Adulto Jovem
12.
Proc Natl Acad Sci U S A ; 121(27): e2314026121, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38917011

RESUMO

The fucosylation of glycoproteins regulates diverse physiological processes. Inhibitors that can control cellular levels of protein fucosylation have consequently emerged as being of high interest. One area where inhibitors of fucosylation have gained significant attention is in the production of afucosylated antibodies, which exhibit superior antibody-dependent cell cytotoxicity as compared to their fucosylated counterparts. Here, we describe ß-carbafucose, a fucose derivative in which the endocyclic ring oxygen is replaced by a methylene group, and show that it acts as a potent metabolic inhibitor within cells to antagonize protein fucosylation. ß-carbafucose is assimilated by the fucose salvage pathway to form GDP-carbafucose which, due to its being unable to form the oxocarbenium ion-like transition states used by fucosyltransferases, is an incompetent substrate for these enzymes. ß-carbafucose treatment of a CHO cell line used for high-level production of the therapeutic antibody Herceptin leads to dose-dependent reductions in core fucosylation without affecting cell growth or antibody production. Mass spectrometry analyses of the intact antibody and N-glycans show that ß-carbafucose is not incorporated into the antibody N-glycans at detectable levels. We expect that ß-carbafucose will serve as a useful research tool for the community and may find immediate application for the rapid production of afucosylated antibodies for therapeutic purposes.


Assuntos
Cricetulus , Fucose , Fucose/metabolismo , Animais , Células CHO , Glicosilação , Humanos , Trastuzumab/farmacologia , Trastuzumab/metabolismo , Fucosiltransferases/metabolismo , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos
13.
Viruses ; 16(5)2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38793666

RESUMO

SARS-CoV-2 primarily infects the lungs via the ACE2 receptor but also other organs including the kidneys, the gastrointestinal tract, the heart, and the skin. SARS-CoV-2 also infects the brain, but the hematogenous route of viral entry to the brain is still not fully characterized. Understanding how SARS-CoV-2 traverses the blood-brain barrier (BBB) as well as how it affects the molecular functions of the BBB are unclear. In this study, we investigated the roles of the receptors ACE2 and DPP4 in the SARS-CoV-2 infection of the discrete cellular components of a transwell BBB model comprising HUVECs, astrocytes, and pericytes. Our results demonstrate that direct infection on the BBB model does not modulate paracellular permeability. Also, our results show that SARS-CoV-2 utilizes clathrin and caveolin-mediated endocytosis to traverse the BBB, resulting in the direct infection of the brain side of the BBB model with a minimal endothelial infection. In conclusion, the BBB is susceptible to SARS-CoV-2 infection in multiple ways, including the direct infection of endothelium, astrocytes, and pericytes involving ACE2 and/or DPP4 and the blood-to-brain transcytosis, which is an event that does not require the presence of host receptors.


Assuntos
Enzima de Conversão de Angiotensina 2 , Astrócitos , Barreira Hematoencefálica , COVID-19 , Dipeptidil Peptidase 4 , Pericitos , SARS-CoV-2 , Transcitose , Internalização do Vírus , Barreira Hematoencefálica/virologia , Barreira Hematoencefálica/metabolismo , Humanos , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/metabolismo , Pericitos/virologia , Pericitos/metabolismo , COVID-19/virologia , COVID-19/metabolismo , Astrócitos/virologia , Astrócitos/metabolismo , Dipeptidil Peptidase 4/metabolismo , Encéfalo/virologia , Encéfalo/metabolismo , Endocitose , Células Endoteliais da Veia Umbilical Humana/virologia , Permeabilidade
15.
Sci Rep ; 14(1): 10431, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714841

RESUMO

Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as "common cold" paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3-11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park. We collected 2047 respiratory symptoms surveys to quantify clinical severity and simultaneously collected 1989 nasopharyngeal swabs approximately monthly for multiplex viral diagnostics. Throughout the course of the study, we also collected 445 faecal samples from 55 wild chimpanzees living nearby in Kibale in social groups that have experienced repeated, and sometimes lethal, epidemics of human-origin respiratory viral disease. We characterized respiratory pathogens in each cohort and examined statistical associations between PCR positivity for detected pathogens and potential risk factors. Children exhibited high incidence rates of respiratory infections, whereas incidence rates in adults were far lower. COVID-19 lockdown in 2020-2021 significantly decreased respiratory disease incidence in both people and chimpanzees. Human respiratory infections peaked in June and September, corresponding to when children returned to school. Rhinovirus, which caused a 2013 outbreak that killed 10% of chimpanzees in a Kibale community, was the most prevalent human pathogen throughout the study and the only pathogen present at each monthly sampling, even during COVID-19 lockdown. Rhinovirus was also most likely to be carried asymptomatically by adults. Although we did not detect human respiratory pathogens in the chimpanzees during the cohort study, we detected human metapneumovirus in two chimpanzees from a February 2023 outbreak that were genetically similar to viruses detected in study participants in 2019. Our data suggest that respiratory pathogens circulate in children and that adults become asymptomatically infected during high-transmission times of year. These asymptomatic adults may then unknowingly carry the pathogens into forest and infect chimpanzees. This conclusion, in turn, implies that intervention strategies based on respiratory symptoms in adults are unlikely to be effective for reducing reverse zoonotic transmission of respiratory viruses to chimpanzees.


Assuntos
Resfriado Comum , Pan troglodytes , Animais , Humanos , Criança , Feminino , Masculino , Pré-Escolar , Resfriado Comum/epidemiologia , Resfriado Comum/virologia , Adulto , Uganda/epidemiologia , Estudos Prospectivos , Zoonoses/epidemiologia , Zoonoses/virologia , COVID-19/epidemiologia , COVID-19/virologia , COVID-19/transmissão , Doenças dos Símios Antropoides/epidemiologia , Doenças dos Símios Antropoides/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/veterinária , Rhinovirus/isolamento & purificação , Rhinovirus/genética , SARS-CoV-2/isolamento & purificação , Incidência
16.
J Surg Res ; 300: 25-32, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38795670

RESUMO

INTRODUCTION: Previous literature suggests that sphingolipids may impact systemic coagulation and platelet aggregation, thus modulating the risks of thrombotic events. The goal of this investigation was to evaluate the role of serum sphingolipids on intrinsic platelet function to assess whether pharmacologic manipulation of sphingolipid metabolites would impact platelet aggregability. METHODS: C57BL/6J mice were injected with either normal saline, 1 mg/kg FTY720 (synthetic sphingosine-1-phosphate [S1P] receptor analog), or 5 mg/kg SLM6031434 (sphingosine kinase two inhibitor). Mice were sacrificed at 6 h and whole blood (WB) was collected for impedance aggregometry assessing platelet responsiveness to arachidonic acid or adenosine diphosphate. Ex vivo studies utilized WB or platelet-rich plasma that was pretreated with S1P, FTY720, amitriptyline, or d-sphingosine then analyzed by aggregability and flow cytometry for platelet and platelet-derived microvesicle characteristics. RESULTS: FTY720 and SLM6031434 pretreated induced similar arachidonic acid and adenosine diphosphate-mediated platelet aggregation as controls. Ex vivo WB and platelet-rich plasma treatment with S1P, FTY720, amitriptyline and d-sphingosine did not impact platelet aggregation. The percentages of CD41+, CD62P+ and CD41+/ceramide+, CD62P+/ceramide + platelets, and platelet-derived microvesicle were not significantly different between amitriptyline-treated and normal saline-treated cohorts. CONCLUSIONS: Sphingolipid modulating agents, such as FTY720, SLM6031434, S1P, amitriptyline, ceramide, and d-sphingosine do not appear to independently impact platelet aggregation in murine models.


Assuntos
Plaquetas , Cloridrato de Fingolimode , Camundongos Endogâmicos C57BL , Agregação Plaquetária , Esfingolipídeos , Esfingosina , Animais , Agregação Plaquetária/efeitos dos fármacos , Cloridrato de Fingolimode/farmacologia , Esfingosina/análogos & derivados , Esfingosina/sangue , Camundongos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Esfingolipídeos/sangue , Esfingolipídeos/metabolismo , Masculino , Lisofosfolipídeos/farmacologia , Lisofosfolipídeos/sangue , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Ácido Araquidônico/farmacologia , Amitriptilina/farmacologia , Difosfato de Adenosina/farmacologia
17.
J Am Vet Med Assoc ; : 1-9, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776968

RESUMO

OBJECTIVE: To determine whether subtotal pericardectomy affects recurrence and long-term outcomes in dogs with idiopathic chylothorax (IC). ANIMALS: 12 client-owned dogs diagnosed with IC between July 26, 2016, and March 23, 2023. METHODS: The diagnosis of constrictive physiology (CP) was established with cardiac catheterization and defined as elevated and equal diastolic pressures in all 4 cardiac chambers. Dogs were then entered into the constrictive physiology (CP) group or non-CP (NCP) group. All dogs received at least a thoracic duct ligation (TDL). The dogs in the CP group had a subtotal pericardectomy performed in addition to TDL. Repeated surgical interventions, recurrence, long-term outcomes, and survival times were recorded. RESULTS: 8 dogs were entered into the CP group and underwent TDL and subtotal pericardectomy. Four dogs were entered in the NCP group and underwent only a TDL. Four dogs in the CP group and 1 in the NCP group required multiple surgeries for recurrent chylothorax. The 1-, 2-, and 3-year disease-free rates were, respectively, 100%, 100%, and 50% for the NCP group and 87.5%, 72.9%, and 72.9% for the CP group (P = .935). The 1-, 2-, and 3-year survival rates were, respectively, 100%, 100%, and 100% for the NCP group and 87.5%, 72.9%, and 72.9% for the CP group (P = .317). CLINICAL RELEVANCE: Constrictive physiology should be evaluated by cardiac catheterization before surgical treatment of IC in dogs. If CP is not diagnosed, subtotal pericardectomy may not be required.

18.
Psychiatr Serv ; : appips20230193, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716514

RESUMO

OBJECTIVE: Although eating disorders are associated with high rates of psychological and physical impairments and mortality, only about 20% of individuals with eating disorders receive treatment. No study has comprehensively assessed treatment access for those with these disorders in the United States. The authors examined access to eating disorder treatments and how it might vary among some populations. METHODS: Seekers of treatment for eating disorders (N=1,995) completed an online assessment of clinical demographic and anthropometric characteristics, barriers to eating disorder treatment access, and eating disorder symptomatology. Analyses were conducted to identify treatment access barriers, compare barriers to treatment access across demographic groups, and investigate relationships between barriers to treatment access and eating disorder symptoms. RESULTS: Financial barriers (e.g., lack of insurance coverage) were the most frequently reported barrier to treatment access. Participants with historically underrepresented identities and with a diagnosis of other specified feeding or eating disorder (OSFED) reported more barriers related to financial challenges, geographic location, eating disorder identification, sociocultural factors, and treatment quality compared with those with historically represented identities (e.g., White and cisgender persons). Higher frequencies of reported barriers to treatment access were associated with more severe eating disorder symptoms and poorer illness trajectories. CONCLUSIONS: Financial barriers were the most significant impediment to accessing treatment among individuals seeking eating disorder treatment. Barriers to treatment access disproportionally affected underrepresented groups and those with an OSFED diagnosis.

19.
Front Pediatr ; 12: 1379131, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756971

RESUMO

Introduction: Respiratory illness is the most common childhood disease globally, especially in developing countries. Previous studies have detected viruses in approximately 70-80% of respiratory illnesses. Methods: In a prospective cohort study of 234 young children (ages 3-11 years) and 30 adults (ages 22-51 years) in rural Western Uganda sampled monthly from May 2019 to August 2021, only 24.2% of nasopharyngeal swabs collected during symptomatic disease had viruses detectable by multiplex PCR diagnostics and metagenomic sequencing. In the remaining 75.8% of swabs from symptomatic participants, we measured detection rates of respiratory bacteria Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae by quantitative PCR. Results: 100% of children tested positive for at least one bacterial species. Detection rates were 87.2%, 96.8%, and 77.6% in children and 10.0%, 36.7%, and 13.3% for adults for H. influenzae, M. catarrhalis, and S. pneumoniae, respectively. In children, 20.8% and 70.4% were coinfected with two and three pathogens, respectively, and in adults 6.7% were coinfected with three pathogens but none were coinfected with two. Detection of any of the three pathogens was not associated with season or respiratory symptoms severity, although parsing detection status by symptoms was challenged by children experiencing symptoms in 80.3% of monthly samplings, whereas adults only reported symptoms 26.6% of the time. Pathobiont colonization in children in Western Uganda was significantly more frequent than in children living in high-income countries, including in a study of age-matched US children that utilized identical diagnostic methods. Detection rates were, however, comparable to rates in children living in other Sub-Saharan African countries. Discussion: Overall, our results demonstrate that nonviral colds contribute significantly to respiratory disease burden among children in rural Uganda and that high rates of respiratory pathobiont colonization may play a role. These conclusions have implications for respiratory health interventions in the area, such as increasing childhood immunization rates and decreasing air pollutant exposure.

20.
J Cutan Pathol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769706

RESUMO

Cytophagic histiocytic panniculitis (CHP) is associated with a number of systemic conditions and is characterized by the presence of benign phagocytic histiocytes ("bean bag cells"), including phagocytosed erythrocytes, leukocytes, and platelets. We describe a case of a 72-year-old female who presented with a papular eruption that clinically mimicked pityriasis lichenoides et varioliformis acuta (PLEVA). Given that her skin biopsy had multiple features concerning PLEVA, this diagnosis was classified as a superficial pityriasis lichenoides-like variant of CHP. The histopathologic presence of cytophagic histiocytosis prompted workup for a systemic malignancy, leading to a diagnosis of underlying acute monocytic leukemia of myeloid lineage.

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